tbuckley/cabot-search huggingface dataset:
Cholinergic sensing of allergen exposure by airway epithelium promotes type 2 immunity in the lungs
Authors: Ryusuke Hayashi, Yotesawee Srisomboon, Koji Iijima, Peter J. Maniak, Rinna Tei, Takao Kobayashi, Mayumi Matsunaga, Huijun Luo, Mia Y. Masuda, Scott M. O’Grady, Hirohito Kita
Journal: Journal of Allergy and Clinical Immunology (2023)
Tertiary Lymphoid Structures Validated as Biomarker
Journal: Cancer Discovery (2023)

New trial data confirm the potential of tertiary lymphoid structures to serve as a predictive biomarker of responsiveness to an immune checkpoint inhibitor-based drug regimen. According to study results presented at the Society for Immunotherapy of Cancer Annual Meeting, treatment with a PD-L1-targeted agent plus a multikinase inhibitor with anti-angiogenic activity yielded clinical responses in patients with TLS-positive tumors, even in cancer types typically considered resistant to checkpoint inhibitors.
Seeking satiety: From signals to solutions
Authors: Matthias H. Tschöp, Jeffrey M. Friedman
Journal: Science Translational Medicine (2023)

Remedies for the treatment of obesity date to Hippocrates, when patients with obesity were directed to “reduce food and avoid drinking to fullness” and begin “running during the night.” Similar recommendations have been repeated ever since, despite the fact that they are largely ineffective. Recently, highly effective therapeutics were developed that may soon enable physicians to manage body weight in patients with obesity in a manner similar to the way that blood pressure is controlled in patients with hypertension. These medicines have grown out of a revolution in our understanding of the molecular and neural control of appetite and body weight, reviewed here.
Direct inhibition of dioxygenases TET1 by the rheumatoid arthritis drug auranofin selectively induces cancer cell death in T-ALL
Authors: Long Chen, Anqi Ren, Yuan Zhao, Hangyu Chen, Qifang Wu, Mengzhu Zheng, Zijian Zhang, Tongcun Zhang, Wu Zhong, Jian Lin, Haichuan Zhu
Journal: Journal of Hematology & Oncology (2023)

Abstract T-cell acute lymphoblastic leukemia (T-ALL) is a type of hematologic tumor with malignant proliferation of hematopoietic progenitor cells. However, traditional clinical treatment of T-ALL included chemotherapy and stem cell transplantation always lead to recurrence and poor prognosis, thus new therapeutic targets and drugs are urgently needed for T-ALL treatment. In this study, we showed that TET1 (ten-eleven translocation 1), a key participant of DNA epigenetic control, which catalyzes the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) to modulate gene expression, was highly upregulated in human T-ALL and negatively correlated with the prognosis of patients. Knockdown of TET1 suppressed T-ALL growth and progression, suggesting that TET1 inhibition maybe an effective way to fight T-ALL via DNA epigenetic modulation. Combining structure-guided virtual screening and cell-based high-throughput screening of FDA-approved drug library, we discovered that auranofin, a gold-containing compound, is a potent TET1 inhibitor. Auranofin inhibited the catalytic activity of TET1 through competitive binding to its substrates binding pocket and thus downregulated the genomic level of 5hmC marks and particularly epigenetically reprogramed the expression of oncogene c-Myc in T-ALL in TET1-dependent manner and resulted in suppression of T-ALL in vitro and in vivo. These results revealed that TET1 is a potential therapeutic target in human T-ALL and elucidated the mechanism that TET1 inhibitor auranofin suppressed T-ALL through the TET1/5hmC/c-Myc signaling pathway. Our work thus not only provided mechanism insights for T-ALL treatment, but also discovered potential small molecule therapeutics for T-ALL.
A retrospective analysis of the gender trajectories of youth who have discontinued a transition
Authors: Annie Pullen Sansfaçon, Élio Gravel, Morgane Gelly, Tommly Planchat, August Paradis, Denise Medico
Journal: International Journal of Transgender Health (2023)

Background: Detransition is frequently covered in the media as a return to a cis identity after transition. Detransition is often studied in isolation and fails to examine it in context of various stages leading to detransition. Aim: To present the perspectives and reflections of youth who have detransitioned on their journey from early transition to discontinuation, focusing on three key dimensions: gender modalities, sexual modalities, and dysphoria experiences, and their evolution during this journey. Method: We drew from 20 in-depth interviews with young people aged 16 to 25 who have discontinued a transition and examined various stages of the gender journey from early transition to detransition. Youth narratives were analyzed thematically and longitudinally. Results: We developed three main themes related to the gender journey: nonlinear gender modalities, navigating sexual modalities along with gender modalities, and coping with dysphoria and body discomfort. We found a great diversity of experiences with regard to these within each participant and across the sample. Discussion: Transition and detransition trajectories are nonlinear and heterogeneous, without any identified commonalities that enable the prediction of outcomes after transitions. However, transnormativity may influence how people who detransition are expected to conform to a certain narrative despite the diversity of experiences present in this community.
Mutations in DEAD/H-box helicase 11 correlate with increased relapse risk in adults with acute myeloid leukaemia with normal cytogenetics
Authors: Ya-Lan Zhou, Ming-Yue Zhao, Robert Peter Gale, Hao Jiang, Qian Jiang, Li-Xia Liu, Jia-Yue Qin, Shan-Bo Cao, Feng Lou, Lan-Ping Xu, Xiao-Hui Zhang, Xiao-Jun Huang, Guo-Rui Ruan
Journal: Leukemia (2023)
Diet-induced shifts in the gut microbiota influence anastomotic healing in a murine model of colonic surgery
Authors: Sonja Boatman, Thomas Kaiser, Harika Nalluri-Butz, Mohammad Haneef Khan, Matthew Dietz, Julia Kohn, Abigail J Johnson, Wolfgang B Gaertner, Christopher Staley, Cyrus Jahansouz
Journal: Gut Microbes (2023)

Host diet and gut microbiota interact to contribute to perioperative complications, including anastomotic leak (AL). Using a murine surgical model of colonic anastomosis, we investigated how diet and fecal microbial transplantation (FMT) impacted the intestinal microbiota and if a predictive signature for AL could be determined. We hypothesized that a Western diet (WD) would impact gut microbial composition and that the resulting dysbiosis would correlate with increased rates of AL, while FMT from healthy, lean diet (LD) donors would reduce the risk of AL. Furthermore, we predicted that surgical outcomes would allow for the development of a microbial preclinical translational tool to identify AL. Here, we show that AL is associated with a dysbiotic microbial community characterized by increased levels of Bacteroides and Akkermansia. We identified several key taxa that were associated with leak formation, and developed an index based on the ratio of bacteria associated with the absence and presence of leak. We also highlight a modifiable connection between diet, microbiota, and anastomotic healing, potentially paving the way for perioperative modulation by microbiota-targeted therapeutics to reduce AL.
Concussion Characteristics in the National Hockey League Before and After the Introduction of Rule 48
Authors: Michael G. Hutchison, Alex P. Di Battista, Willem Meeuwisse, Jared M. Bruce, Ruben J. Echemendia, J. Scott Delaney, Paul Comper
Journal: JAMA Network Open (2023)

Importance A rule prohibiting a direct hit to the lateral side of the head (ie, Rule 48–Illegal Check to the Head) was introduced in the National Hockey League (NHL) in the 2010-2011 season and refined in the 2011-2012 season to widen the application to include direct contact to all areas of the head. Objective To compare the incidence and proportion of concussions that occurred following hits to the head before and after the implementation of Rule 48. Design, Setting, and Participants This retrospective cohort study used a before and after design to evaluate concussions among NHL players in regular season games. Data from the 4 seasons preceding the implementation of Rule 48 (2006-2007 to 2009-2010) were compared with data from 5 seasons following its implementation (2014-2015 to 2018-2019). Data were analyzed from October 31, 2021, to November 30, 2022. Main Outcomes and Measures The incidence and relative proportion of concussion characteristics and mechanisms before and after the introduction of Rule 48. Results In the analysis of 688 concussions for NHL seasons spanning 2006 to 2010 (n = 231) and 2014 to 2019 (n = 457), there was an overall increase in the incidence of concussion between the 2 time frames, although the incidence of concussions due to hits to the lateral aspect of the head decreased from 1.6/100 games to 1.0/100 games (estimated difference, 0.6/100 games [90% credible interval (CrI), 0.30/100 games to 0.90/100 games). There was also a reduction of 18.8 (90% CrI, 13.0-23.7) percentage points in the proportion of concussions due to hits to the lateral aspect of the head from 80 of 231 concussions (34.6%) to 61 of 457 concussions (13.3%). The incidence of concussions following hits to the head from body checks using the shoulder, arm, and glove was similar before and following the implementation of Rule 48. However, the proportion was reduced 14.7 percentage points from 113 of 231 concussions (48.9%) before to 149 of 457 concussions (32.6%) after implementation of Rule 48 (90% CrI of the difference, 8.9-20.7 percentage points). Conclusions and Relevance The findings of this cohort study of NHL players suggest that after the introduction of Rule 48, the incidence rate and proportion of concussions from contact to the lateral aspect of the head decreased, as did the proportion of concussions following direct hits to the head.
Implications of Exome Sequencing for Patients With Congenital Hydrocephalus
Authors: Abhaya V. Kulkarni
Journal: JAMA Network Open (2023)

Ana B. W. Greenberg, BS; Neel H. Mehta, BA; Garrett Allington, PhD; Sheng Chih Jin, PhD; Andrés Moreno-De-Luca, MD; Kristopher T. Kahle, MD, PhD
System-Level Factors and Time Spent on Electronic Health Records by Primary Care Physicians
Authors: Lisa S. Rotenstein, A. Jay Holmgren, Daniel M. Horn, Stuart Lipsitz, Russell Phillips, Richard Gitomer, David W. Bates
Journal: JAMA Network Open (2023)

Primary care physicians (PCPs) spend the most time on the electronic health record (EHR) of any specialty. Thus, it is critical to understand what factors contribute to varying levels of PCP time spent on EHRs.
High-Sensitivity vs Conventional Troponin Cutoffs for Risk Stratification in Patients With Acute Pulmonary Embolism
Authors: Behnood Bikdeli, Alfonso Muriel, Carmen Rodríguez, Sara González, Winnifer Briceño, Ghazaleh Mehdipoor, Gregory Piazza, Aitor Ballaz, Giuseppe Lippi, Roger D. Yusen, Remedios Otero, David Jiménez
Journal: JAMA Cardiology (2023)

High-sensitivity troponin tests can detect even milder cardiac troponin elevations in plasma, beyond the threshold of conventional troponin tests. Whether detection of low-grade cardiac troponin elevation is associated with outcomes of patients with hemodynamically stable pulmonary embolism (PE) and helps with risk stratification is unknown.
Assessing Response for Nivolumab Plus Ipilimumab in Squamous Cell Carcinoma of the Head and Neck—Reply
Authors: Kevin J. Harrington, Robert Haddad
Journal: JAMA Oncology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Assessing Response for Nivolumab Plus Ipilimumab in Squamous Cell Carcinoma of the Head and Neck
Authors: Oliver Klein
Journal: JAMA Oncology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
First-Line Osimertinib for Previously Untreated Patients With NSCLC and Uncommon <i>EGFR</i> Mutations
Authors: Yusuke Okuma, Kaoru Kubota, Mototsugu Shimokawa, Kana Hashimoto, Yosuke Kawashima, Tomohiro Sakamoto, Hiroshi Wakui, Shuji Murakami, Kyoichi Okishio, Kenji Hayashihara, Yuichiro Ohe
Journal: JAMA Oncology (2023)

Non-small cell lung cancer (NSCLC) with uncommon EGFR mutations is a rare subgroup, composing 14% of all EGFR mutations.
<i>Notes from the Field:</i> Diagnosis of Congenital Syphilis and Syphilis Among Females of Reproductive Age Before and During the COVID-19 Pandemic — Chicago, 2015–2022
Authors: Helen E. Cejtin, Eric F. Warren, Taylor Guidry, Katherine Boss, Ashley Becht, Irina Tabidze
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Syphilis is a bacterial infection that is of particular concern during pregnancy because of the risk for transplacental fetal infection.Pregnancies complicated by untreated syphilis are at increased risk for adverse outcomes, including stillbirth and long-term physical and cognitive sequelae in the affected infant.After implementation of enhanced efforts ( 1) by the Chicago Department of Public Health (CDPH) to eliminate congenital syphilis, including improvements to the surveillance and case management system, the number of Chicago congenital syphilis cases steadily decreased during 2015-2019, despite national increases in congenital syphilis and local increases in syphilis among females of reproductive age.*In 2020, with the emergence of the COVID-19 pandemic, the trend in Chicago abruptly shifted, and cases of congenital syphilis increased during the next 3 years.* Females of reproductive age are persons aged 15-44 years and assigned female sex at birth.CDPH, deemed not research, and was conducted consistent with applicable federal law and CDC policy.†
A Cluster of Ocular Syphilis Cases with a Common Sex Partner — Southwest Michigan, 2022
Authors: William D. Nettleton, James B. Kent, Karen Lightheart, Jill C. Diesel
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Untreated syphilis can lead to ocular syphilis, otosyphilis, and neurosyphilis, conditions resulting from Treponema pallidum infection of the eye, inner ear, or central nervous system. During March-July 2022, Michigan public health officials identified a cluster of ocular syphilis cases. The public health response included case investigation, partner notification, dissemination of health alerts, patient referral to a public health clinic for diagnosis and treatment, hospital care coordination, and specimen collection for T. pallidum molecular typing. Five cases occurred among southwest Michigan women, all of whom had the same male sex partner. The women were aged 40-60 years, HIV-negative, and identified as non-Hispanic White race; the disease was staged as early syphilis, and all patients were hospitalized and treated with intravenous penicillin. The common male sex partner was determined to have early latent syphilis and never developed ocular syphilis. No additional transmission was identified after the common male partner's treatment. Due to lack of genetic material in limited specimens, syphilis molecular typing was not possible. A common heterosexual partner in an ocular syphilis cluster has not been previously documented and suggests that an unidentified strain of T. pallidum might have been associated with increased risk for systemic manifestations of syphilis. A high index of clinical suspicion and thorough sexual history are critical to diagnosing ocular syphilis, otosyphilis, and neurosyphilis. Coordination of disease surveillance with disease intervention specialist investigation and treatment referral can interrupt syphilis transmission.
Osimertinib in Patients With Non–Small Cell Lung Cancer and Uncommon <i>EGFR</i> Mutations—Chasing Unicorns?
Authors: Victoria E. Wang, Justin F. Gainor
Journal: JAMA Oncology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Massive underrepresentation of Arabs in genomic studies of common disease
Authors: Romit Bhattacharya, NingNing Chen, Injeong Shim, Hiroyuki Kuwahara, Xin Gao, Fowzan S. Alkuraya, Akl C. Fahed
Journal: Genome Medicine (2023)

Abstract Arabs represent 5% of the world population and have a high prevalence of common disease, yet remain greatly underrepresented in genome-wide association studies, where only 1 in 600 individuals are Arab. We highlight the persistent and unaddressed underrepresentation of Arabs in genomic databases and discuss its impact on public health genomics and missed opportunities for biological discovery.
PRMT1 Inhibition Activates the Interferon Pathway to Potentiate Antitumor Immunity and Enhance Checkpoint Blockade Efficacy in Melanoma
Authors: Hongru Tao, Chen Jin, Liyuan Zhou, Zhenzhong Deng, Xiao Li, Wenzhen Dang, Shijie Fan, Bing Li, Fei Ye, Junyan Lu, Xiangqian Kong, Chuanpeng Liu, Cheng Luo, Yuanyuan Zhang
Journal: Cancer Research (2023)

Despite the immense success of immune checkpoint blockade (ICB) in cancer treatment, many tumors, including melanoma, exhibit innate or adaptive resistance. Tumor-intrinsic T-cell deficiency and T-cell dysfunction have been identified as essential factors in the emergence of ICB resistance. Here, we found that protein arginine methyltransferase 1 (PRMT1) expression was inversely correlated with the number and activity of CD8+ T cells within melanoma specimen. PRMT1 deficiency or inhibition with DCPT1061 significantly restrained refractory melanoma growth and increased intratumoral CD8+ T cells in vivo. Moreover, PRMT1 deletion in melanoma cells facilitated formation of double-stranded RNA derived from endogenous retroviral elements (ERV) and stimulated an intracellular interferon response. Mechanistically, PRMT1 deficiency repressed the expression of DNA methyltransferase 1 (DNMT1) by attenuating modification of H4R3me2a and H3K27ac at enhancer regions of Dnmt1, and DNMT1 downregulation consequently activated ERV transcription and the interferon signaling. Importantly, PRMT1 inhibition with DCPT1061 synergized with PD-1 blockade to suppress tumor progression and increase the proportion of CD8+ T cells as well as IFNγ+CD8+ T cells in vivo. Together, these results reveal an unrecognized role and mechanism of PRMT1 in regulating antitumor T-cell immunity, suggesting PRMT1 inhibition as a potent strategy to increase the efficacy of ICB.
Lab‐on‐a‐Fiber Wearable Multi‐Sensor for Monitoring Wound Healing
Authors: Giorgia Giovannini, Khushdeep Sharma, Luciano F. Boesel, René M. Rossi
Journal: Advanced Healthcare Materials (2023)

Abstract Chronic wounds are regarded as a silent epidemic, affecting 1–2% of the population and representing 2–4% of healthcare expenses. The current methods used to assess the wound healing process are based on the visual evaluation of physical parameters. This work aims to design a wearable non‐invasive device capable of evaluating three parameters simultaneously: the pH and the levels of glucose and matrix metalloproteinase (MMP) present in the wound exudate. The device is composed of three independent polymer optical fibers functionalized with fluorescent‐based sensing chemistries specific to the targeted analytes. Each fiber is characterized in terms of detection sensitivity and selectivity confirming their suitability for monitoring the targeted parameters in ranges relevant to the wound environment. The selectivity and robustness of the multi‐sensing device are confirmed with analyses using complex solutions with different pH levels (5, 6, and 7), different concentrations of glucose (1.25, 2.5, and 5 m m ), and MMP (1.25, 2.5, and 5 µg mL −1 ). Given the simple set‐up, the affordability of the materials used and the possibility of detecting additional parameters relevant to wound healing, such multi‐sensing fiber‐based devices could pave the way for novel non‐invasive wearable tools enabling the assessment of wound healing from the molecular perspective.